rs2070534

Variant names:

• chr21-43755489-G-A
• rs2070534
• NM_003681.5:c.760-209G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003681.5(PDXK):​c.760-209G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 585,418 control chromosomes in the GnomAD database, including 31,346 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.33 (8095 hom., cov: 34)
  • Exomes 𝑓: 0.32 (23251 hom.)
• Consequence: PDXK NM_003681.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.19
• Publications: 3 publications found

Genes affected

PDXK (HGNC:8819): (pyridoxal kinase) The protein encoded by this gene phosphorylates vitamin B6, a step required for the conversion of vitamin B6 to pyridoxal-5-phosphate, an important cofactor in intermediary metabolism. The encoded protein is cytoplasmic and probably acts as a homodimer. Alternatively spliced transcript variants have been described, but their biological validity has not been determined. [provided by RefSeq, Jul 2008]

PDXK Gene-Disease associations (from GenCC):

• neuropathy, hereditary motor and sensory, type VIc, with optic atrophy

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 21-43755489-G-A is Benign according to our data. Variant chr21-43755489-G-A is described in ClinVar as Benign. ClinVar VariationId is 1175405.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.471 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003681.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	NM_003681.5	MANE Select	c.760-209G>A		intron	N/A	NP_003672.1	O00764-1
	PDXK	NM_001331030.2		c.640-209G>A		intron	N/A	NP_001317959.1	F2Z2Y4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PDXK	ENST00000291565.9	TSL:1 MANE Select	c.760-209G>A		intron	N/A	ENSP00000291565.4	O00764-1
	PDXK	ENST00000468090.5	TSL:1	c.676-209G>A		intron	N/A	ENSP00000418359.1	O00764-2
	PDXK	ENST00000343528.10	TSL:1	n.730-209G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49464 AN: 152092 Hom.: 8090 Cov.: 34

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.482

Gnomad AMR AF: 0.380

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.487

Gnomad SAS AF: 0.343

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.302

Gnomad OTH AF: 0.351

GnomAD4 exome AF: 0.324 AC: 140226 AN: 433208 Hom.: 23251 Cov.: 3 AF XY: 0.324 AC XY: 73793 AN XY: 228108

African (AFR) AF: 0.318 AC: 3847 AN: 12088

American (AMR) AF: 0.385 AC: 7031 AN: 18248

Ashkenazi Jewish (ASJ) AF: 0.343 AC: 4517 AN: 13164

East Asian (EAS) AF: 0.451 AC: 13587 AN: 30118

South Asian (SAS) AF: 0.340 AC: 15372 AN: 45270

European-Finnish (FIN) AF: 0.281 AC: 8032 AN: 28564

Middle Eastern (MID) AF: 0.297 AC: 569 AN: 1916

European-Non Finnish (NFE) AF: 0.306 AC: 79123 AN: 258826

Other (OTH) AF: 0.326 AC: 8148 AN: 25014

GnomAD4 genome AF: 0.325 AC: 49499 AN: 152210 Hom.: 8095 Cov.: 34 AF XY: 0.327 AC XY: 24347 AN XY: 74416

African (AFR) AF: 0.322 AC: 13354 AN: 41524

American (AMR) AF: 0.379 AC: 5807 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1143 AN: 3470

East Asian (EAS) AF: 0.487 AC: 2518 AN: 5170

South Asian (SAS) AF: 0.342 AC: 1648 AN: 4822

European-Finnish (FIN) AF: 0.305 AC: 3232 AN: 10600

Middle Eastern (MID) AF: 0.298 AC: 87 AN: 292

European-Non Finnish (NFE) AF: 0.302 AC: 20523 AN: 68002

Other (OTH) AF: 0.354 AC: 748 AN: 2114

Alfa AF: 0.300 Hom.: 919

Bravo AF: 0.336

Asia WGS AF: 0.382 AC: 1332 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.91
DANN	Benign	0.50
PhyloP100		-2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2070534; hg19: chr21-45175370;